Abstract Mechanism by which lipopolysaccharide (LPS) and interferon γ (IFNγ) downregulate smooth muscle (SM) α-actin expression in rat hepatic stellate cell was studied. Culture-induced SM α-actin expression was suppressed in the presence of LPS (> 5 ng/ml) and/or IFNγ (> 1 U/ml) dose-dependently. Inhibition of nitric oxide (NO) production by Nω-nitro-L-arginine (LNA) canceled such an inhibitory effect of LPS and/or IFNγ. LPS and/or IFN γ increased cellular level of cGMP in an LNA inhibitable manner, and cGMP analogues attenuated SM α-actin expression of the cells. These results indicate that NO-dependent increase of cellular cGMP level mediates the inhibitory effect of LPS and IFNγ on SM α-actin expression in stellate cells.