The purpose of this study was to observe the THP-1 cytokine response induced by different virulent Leptospira strains and evaluate the role of innate immune in the pathogenesis of leptospirosis. THP-1 induced by phorbol myristoyl acetate were incubated with three different Leptospira strains, the virulent Leptospira interrogans serovar Lai type strain Lai, the avirulent L. interrogans serovar Lai type strain IPAV, and the nonpathogenic L. biflexa serovar Patoc type strain Patoc 1 respectively. Cells and supernatant infected by leptospires were collected at 0、2、12、24 and 48 hours post inoculation. The mRNA and protein levels of TNF-α、IFN-γ、IL-12、MCP-1 were quantified by real-time RT-PCR and ELISA. Meanwhile, real-time RT-PCR was used to detected mRNA levels of TLR2、TLR4 and iNOS of THP-1 infected by leptospires. It was found that Lai type strain Lai and Lai type strain IPAV can induce THP-1 TLR4 and iNOS expression in mRNA levels, but Patoc type strain Patoc 1 can induce THP-1 TLR2, TLR4 and iNOS expression in mRNA levels. The level of the THP-1 cytokine TNF-α、IFN-γ、IL-12、MCP-1 inoculation with strain Lai was lower than that inoculation with strain IPAV and strain Patoc 1 neither the level of mRNA nor protein. Thus the virulent strain Lai induces low 1evels of cytokines may be precipitate to escape of the host immune response and spreading.