Objective To investigate the effect of lipopolysaccharide (LPS) on the activation of mouse lung fibroblasts. Methods Primary cultured mouse lung fibroblasts were incubated in 96 well plates and randomly divided into 2 groups: control group ( group C, n = 6) and LPS group ( n = 24). The fibroblasts were cultured for 72 h in group C. LPS 1 μg/ml was added and then the fibroblasts were incubated for 72 h in group LPS. The expression of type Ⅰ procollagen mRNA, α-smooth muscle actin (α-SMA) mRNA, Toll-like receptor 4 (TLR4)mRNA and integrin β1 mRNA was determined using real-time PCR at 3, 6, 24 and 72 h of incubation (6 wells at each time point). Results Compared with group C, there was no significant change in the expression of type Ⅰ procollagen mRNA, α-SMA mRNA, TLR4 mRNA and integrin β1 mRNA at 3, 6 and 24 h of incubation ( P >0.05), but the parameters mentioned above were significantly up-regulated at 72 h of incubation in group LPS ( P < 0.05). Conclusion In the early acute lung injury, LPS leads to pulmonary fibrosis through activating lung fibroblasts directly, and also accelerates the activation of lung fibroblasts and promotes the process of pulmonary fibrosis through up-regulating the expression of TLR4 and integrin β1 in mice. Key words: Lipopolysaccharides; Fibroblasts; Cell survival; Lung