Objective To investigate the effect of fluvastatin on activation of nuclear factor kappa B（NF-κB）induced by angiotensin Ⅱ (AngⅡ) in rat kidney tubular epithelial cells (NRK-52E). Methods NRK-52E cells were divided into （1）control group；（2）AngⅡgroups with different concentration and time；（3）AngⅡ（10-6 mol/L）+SB203580 （10 μmol/L）group；（4）AngⅡ（10-6 mol/L） +different fluvastatin concentration （10-7, 10-6, 10-5 mol/L）groups；(5)AngⅡ（10-6 mol/L） +fluvastatin （10-5 mol/L） +mevalonate （10-4 mol/L）group. Electrophoretic mobility shift assays (EMSA) was used to detect NF-κB activation. Phosphorylation of cellular p38 mitogen-activated protein kinase (p38MAPK) was determined by Western blot. Monocyte chemoattractant protein (MCP)-1 mRNA was determined by RT-PCR. Results AngⅡ stimulated the DNA-binding activity of NF-κB，phosphorylation of p38MAPK and up-regulated the expression of MCP-1 mRNA in cultured NRK-52E cells in a dose-dependent manner(P<0.01). Ang Ⅱ(10-6 mol/L) induced a rapid (5 minutes) elevation of the p38MAPK phosphorylation. NF-κB DNA binding activity was increased at as early as 30 minutes(P<0.01), peaked at 2 hours after AngⅡ treatment(P<0.01). This stimulatory effect of AngⅡ on NF-κB was blocked by SB203580 (a specific inhibitor of p38MAPK) (P<0.01). Incubation of cells with fluvastatin significantly inhibited the AngⅡ-induced NF-κB activation and expression of MCP-1 mRNA in dose-dependent manner (P<0.05). Exogenous mevalonate (10-4 mol/L) prevented the effect of fluvastatin on NF-κB activation (P<0.05). Conclusions Fluvastatin reduces AngⅡ-induced NF-κB activation via the p38MAPK pathway in NRK-52E cells. Such effect of flurastatin is partly through blocked by mevalonate.