This study is set to explore the role of commonly used intravenous anesthetic propofol on the inflammatory response of rat liver Kupffer cells (KCs) induced by lipopolysaccharides (LPS). The isolated KCs were cultured at the density of 1 × 10(5)/ml, divided into five groups randomly after 48 h culture: group C, control group; group L, KCs were treated with 1 μg/ml LPS for 24 h; groups P1, P2, P3, KCs were pretreated with propofol at low (25 μM), medium (50 μM), high (100 μM) concentration for 2 h, respectively, and then were stimulated with 1 μg/ml LPS for 24 h. The expressions of tumor necrosis factor-α (TNF-α) mRNA and interleukin-1β (IL-1β) mRNA of every group were measured by RT-PCR. Nuclear NF-ΚB p65 was determined by Western blot. The concentrations of IL-1β and TNF-α in supernatant were measured by ELISA. Compared with the group C, TNF-α mRNA and IL-1β mRNA in group L were significantly up-regulated and NF-ΚB p65 was significantly up-regulated after LPS treatment (P < 0.05). Meanwhile, TNF-α and IL-1β were also significantly increased (P < 0.05). With propofol the mRNA expressions of aforementioned inflammatory mediators were significantly down-regulated and NF-ΚB p65 was significantly inhibited in group P2 and P3 (P < 0.05), compared with group L. However, low propofol concentration did not exhibit any effect (group P1, P > 0.05). Propofol at medium and high concentration can counteract the LPS-induced inflammatory response in KCs by regulating NF-ΚB p65 protein expression.