The neuropeptide ${alpha}$-melanocyte-stimulating hormone (${alpha}$-MSH) has anti-inflammatory property by down regulating the expressions of proinflammatory cytokines. Because ${alpha}$-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes ${alpha}$-MSH (L. casei-${alpha}$-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the ${alpha}$-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and ${alpha}$-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-${alpha}$-MSH on the colitis, L. casei or L. casei-${alpha}$-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-${alpha}$-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: $14.45{pm}0.2;g$; L. casei-${alpha}$-MSH: $18.2{pm}0.12;g$), colitis score (DSS alone: $3.6{pm}0.4$; L. casei-${alpha}$-MSH: $1.4{pm}0.6$), MPO activity (DSS alone: $42.7{pm}4.5;U/g$; L. casei-${alpha}$-MSH: $10.25{pm}0.5;U/g$), survival rate, and histological damage compared with the DSS alone mice. L. casei-${alpha}$-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and $NF-{kappa}B$ activation. The ${alpha}$-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.