Even fed with the identical diet after weaning, SL animals maintained higher body weight throughout life. Additionally, significant glucose intolerance, and hyperleptinemia were observed in adult SL animals. These results are generally in accordance with earlier studies. The effects of obesity on pulmonary function have been extensively studied by Shore’s group with genetic and diet-induced obesity in mice. However, the influence of obesity duration on respiratory system has rarely been investigated. In order to study this, we chose two time points: P21 and P150, and mice at these ages are generally equivalent to young and adult in human, respectively. In our neonatal overfeeding induced obesity model, AHR was only observed in adult mice. At obese state, lung volumes and expiratory flow rates were reduced. What surprised us is that airway responsiveness did not differ between neonatal overfeeding and control group on P21 though obvious difference in body weight has already existed. This could possibly be attributable to the fact that duration of obesity GSK1120212 determines the development of AHR. These findings were supported by several other literatures. For instance, Cpefat mice had average body weight 23% and 84% more than controls at 7 and 14 weeks of age, whereas AHR was only found at 14 weeks ; and diet-induced obesity mice also displayed enhanced AHR in the older mice. Furthermore, our study is consistent with some of the clinical observations that obese children younger than 5 years old did not show significant changes in pulmonary function. All these findings suggest that extended duration of obesity is required to elicit subsequent AHR. Airway inflammation is a critical factor contributing to AHR in the development of asthma. In our study, more infiltrated inflammatory cells, especially macrophages as demonstrated by F4/80 immunohistochemistry, were observed in peri-bronchiolar areas and alveolar interstitium of neonatal overfeeding mice on P150; however, these changes were not found on P21. The same change was present in BALF cell counting, showing that total cells and classified cells of BALF were significantly increased in neonatal overfeeding mice on P150. Though the classified cells of BALF in neonatal overfeeding mice on P21 were higher than their counterparts at the same period, the total cells of BALF were far fewer than those on P150. Therefore, our results suggest that neonatal overfeeding could induce macrophage recruitment, and these activated alveolar macrophages may increase pulmonary disease susceptibility. Macrophage recruitment in the lungs of obese subjects may subsequently result in lymphocyte accumulation. It is the reason why the lymphocytes increased followed by macrophages. However, our results were different from Lu’s reports, which showed that db/db mice exhibited AHR but BALF inflammatory cells were not significantly different from lean mice after air exposure. After challenged with ovalbumin, inflammatory cells from ob/ob mice were increased in the lung tissue to greater extent than wide-type mice, but the extent of increase in BALF was still lower than wild-type mice. One potential explanation for this disparity is the role of leptin, which could promote inflammatory cells in the lungs migrating into airway lumen. Ob/ob and db/db mice are genetically deficient in either leptin or leptin receptor, leading to the absence of anorexigenic and pro-inflammatory capacity of leptin.