Pulmonary inflammation were reported in several lipid metabolism related gene knock out mice. However, the effects of high fat/high cholesterol diet induced dyslipidemia on the homeostasis of wild C57BL/6J mice lung were poorly understood. 6-8 week-old male C57BL/6J mice were randomly divided into two groups and received either regular diet (RD) containing 10%kcal fat or high fat/high cholesterol diet (HCD) with 40%kcal fat, 1.25% cholesterol and 0.5% sodium cholate respectively. After 16 weeks feeding, mice were anaesthetised with pentobarbital (50mg/ kg, i.p.), and then euthanized by exsanguination from heart. Measured by autobiochemistry analyzer, Serum lipids results showed that hypercholesterolemia was induced in 16 weeks HCD fed C57BL/6J mice (Serum total cholesterol: 5.14±0.37 vs. 3.74±0.23 mmol/L, p<0.05, n=3; Serum low density lipoprotein: 3.35±0.41 vs. 0.46±0.06 mmol/L, p<0.01, n=3; HCD group vs. RD group). Values are means ± S.E.M, compared by student’s t test. Oil red O staining demonstrated that pulmonary lipid accumulation was progressively exacerbated in HCD fed C57BL/6J mice. Hematoxylin and eosin (H&E) and immunohistochemistry studies showed distinctive signs of pulmonary inflammation including macrophage accumulation, lymphocyte infiltration and elevated levels of proinflammatory cytokines like MCP1. (Bronchoalveolar lavage fluid MCP levels HCD group vs. RD group: 110.83±0.79 vs. 81.78±3.69 pg/ml, p<0.01, n=3). Consistently, real-time quantitative PCR and western blotting results showed the mRNA and protein expressions of TLR2 and TLR4 were significantly up-regulated. (mRNA levels of TLR2 and TLR4 in the lungs of HCD group mice were elevated 8.13±0.39 and 3.78±0.23 folds respectively, compared to RD group mice. p<0.05, n=3). Meanwhile, the translocation of NFkappaB into nucleus was activated in high fat/high cholesterol diet fed mice lung. Our findings suggested that high fat/high cholesterol diet could promote lipid accumulation and inflammation in the lung of C57BL/6J mice, which may partly due to the activation of TLRs/ NFkappaB pathway triggered by disturbance of lipid metabolism in the lung.