Leptospirosis is a re‐emerging infectious disease, affecting both animals and humans worldwide. Multiple organ involvement may be encountered in leptospirosis, and early renal involvement is very common, characterized by tubulo‐interstitial nephritis and tubular dysfunction. All 12 patients diagnosed in Chang Gung Memorial Hospital (Taiwan) between 1997 and 1999 had acute renal failure, with five patients requiring dialysis. Leptospira shermani is the main serovar encountered in Taiwan, and penicillin may dramatically rescue patients from multiple organ failure provided it is given early. To understand the mechanism behind tubular injuries by leptospira infection, outer membrane proteins (OMPs) extracted from pathogenic leptospira were given to tubular cells in culture. Our in vitro experiment showed that OMPs of pathogenic leptospira activate nuclear NF κ B binding and stimulate downstream inducible nitric oxide (iNOS), monocyte chemoattractant protein‐1 (MCP‐1) and tumor necrosis factor‐ α (TNF‐ α ) expression. These results indicate that leptospiral infection may induce tubulo‐interstitial nephritis through a toxic component in the outer membrane followed by expression of inflammatory genes.