BACKGROUND: Propofol has an antioxidant capacity and can be used for ischemia-reperfusion injury of the liver. However, the effects of propofol on the Kupffer cells have not been established. METHODS: Kupffer cells were isolated and cultured from male Sprague-Dawley rats. The effects of propofol on the Kupffer cells were evaluated by a phagocytosis assay, TNF-alpha gene expression, TNF-alpha production, and superoxide anion release after administering propofol in different concentrations on the cultured Kupffer cells. RESULTS: The latex bead phagocytosis by the Kupffer cells was suppressed when the Kupffer cells were exposed to propofol irrespective of concentrations. Higher propofol concentrations decreased the loss of Kupffer cells after latex bead phagocytosis. Propofol induced TNF-alpha mRNA expression in the Kupffer cells, but the mRNA expression level after 50microgram/ml of propofol decreased. The pattern of TNF-alpha mRNA expression induced by propofol was different to that induced by LPS: TNF-alpha mRNA was expressed continuously in the propofol-treated cells until 16 hours after exposure to propofol, whereas the level of TNF-alpha mRNA expression induced by LPS was evident after 2 hours and was not found thereafter. TNF-alpha production after propofol treatment was not higher than that of the control. Formazan precipitation did not show any qualitative differences between cells untreated or treated with propofol concentrations of 0.5, 5.0, and 50microgram/ml. CONCLUSIONS: These results showed that propofol might inhibit Kupffer cells. This suggests that propofol can be used for patients with ischemia-reperfusion injury of the liver.