Aim To explore the effects of NOD1/receptor-interacting protein 2(RIP2) signal pathway on macrophage inflammatory activation and phenotype by human monocytic cell line THP-1. Methods Human THP-1 cells were differentiated into macrophages by addition of 160 nmol/l phorbol 12-myristate 13-acetate (PMA) for 24 h. Macrophages were incubated with different concentrations of ox-LDL(0,5, 50 mg/L) for 24 h. The expression of NOD1 and RIP2 was detected by RT-PCR and Western blot. ELISA was used to detect the secretion of monocyte chemotactic protein 1 (MCP-1) and macrophage migration inhibition factor (MIF). FACS was used to detect membrane molecule CDl6/CD68. Results ox-LDL could up-regulate the expression of NOD1/RIP2 signal pathway as a dose-dependent manner in THP-1 derived macrophages. The expression of NOD1, RIP2 mRNA and protein was up-regulated followed the increasing concentrations of ox-LDL. Activation of NOD1 /RIP2 signaling pathway increased the expression of MCP-1 and MIF from the cell culture supernatants. With the increasing concentrations of ox-LDL, the secretion of MCP-1 and MIF increased(P<0.05). The activation of NOD1/RIP2 signaling pathway could change the expression of membrane molecule CD16/CD68. With the different ox-LDL concentrations, the mean fluorescence intensity of CD16/CD68 varied. 50 mg/L group could significantly reduce the expression of CD16/CD68(P<0.01). Conclusion ox-LDL can up-regulate the expression of NOD1/RIP2 signal pathway in a dose-dependent manner in macrophages. NOD1/RIP2 signal pathway enables the macrophage inflammatory activation and polarity switch, which may be the main mechanism in the initiation and progression of atherosclerosis.