Oral intake of some lactic acid bacteria can have beneficial effects on the host by activating immune responses and enhancing resistance to infection by pathogens. In this study, effects of Lactobacillus sp. on the development of autoimmune disease were examined in mice with collagen-induced arthritis (CIA). CIA, a model of some types of rheumatoid arthritis (RA), can be induced in DBA/1J mice by immunizing them with bovine type II collagen (bCII). Oral intake of skimmed milk (SM) fermented with Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (SM/OLL1073R-1) was found to markedly inhibit the development of CIA in these mice, compared with a control group fed the control foodstuff. The inhibitory effect of SM fermented with L. delbrueckii subsp. bulgaricus OLLI 102 (SM/OLL1102) or fresh SM was weaker than that of SM/ OLL1073R-1. A deMan Rogosa Sharpe (MRS) broth culture of OLL1073R-1 without any major components of SM had the same inhibitory effect as SM/OLL1073R-1, suggesting that the inhibitory effect of SM/OLL1073R-1 is attributable not only to SM components but also to OLL1073R-1 cells, their metabolites, or both. We found that SM/OLL1073R-1 and SM caused reduced secretion of the cytokine IFN-gamma by lymph node cells (LNCs) in response to bCII. However, SM/OLL1102 did not affect the secretion of IFN-gamma. A polysaccharide fraction secreted by OLL1073R-1 also exhibited the inhibitory effects on both development of CIA and secretion of IFN-gamma.