Objective: To examine whether lipoxin A4 (LXA4) has an inhibitory effect on tumor necrosis factor-α(TNF-α)-induced proliferation of glomerular mesangial cells of rat, and explore the molecular mechanisms of signal pathway in LXA4 actions. Methods: Glomerular mesangial cells of rat were cultured and treated with TNF- α(10 ng/ml),with or without preincubation with LXA4 at different concentrations. Cell proliferation was evaluated by monotetrazolium (MTr) colorimetric assay. The expression of cyclin E mRNA was measured by RT-PCR. Phosphorylated Akt1 (Thr308) and p27kip1 were analyzed by Western blotting. Results: TNF- α- stimulated proliferation of mesangial cells was inhibited by LXA4 in a dose-dependent manner. The marked increments in cyclin E mRNA expression induced by TNF-α during proliferation of mesangial cells were down-regulated by LXA4. Threonine phosphorylated Akt1 proteins at 308 site stimulated by TNF-α was reduced by LXA4. TNF-α-induced decrements in expression of p27kip1 proteins was ameliorated by LXA4 in a dose-dependent manner. Conclusion: TNF-α-induced proliferation of rat mesangial cells can be inhibited by TXA4 through the mechanism of Akt1/p27kip1 pathway-dependent signal transduction.