The anti-obesity effects of dead Lactobacillus plantarum nF1 (nLp), live Lactobacillus plantarum pF1 (pLp), or live Lactobacillus plantarum PNU (PNU) were studied on C57BL/6 mice fed a 45% high-fat diet. The body, liver, and epididymal fat weights of mice fed nLp were significantly lower than those of mice in the pLp, PNU, or control groups (P<0.05). Serum triglyceride, total cholesterol, glucose, and insulin levels were significantly lower in the nLp, pLp, or PNU groups than in control, and these levels were significantly lower in the nLp group than in the pLp and PNU groups (P<0.05). On the other hand, adiponectin and HDL-cholesterol levels were significantly higher in the nLp group than in the pLp, PNU, and control groups. Histological observations indicated that nLp reduced fat accumulation in liver tissue. Furthermore, L. plantarum strains significantly reduced the mRNA expressions of SREBP-1c, increased the mRNA levels of PPAR-α, CPT-1, and ACO in liver tissues, and significantly increased the mRNA levels of PPAR-α, and CPT-1 in epididymal fat tissues. In particular, the mRNA expressions of PPAR-α and CPT-1 in liver and epididymal fat tissues were highest in the nLp group. These results suggest that nLp (dead L. plantarum) has a greater anti-obesity effect on high-fat diet-induced mice than the live strain (pLp) and a live L. plantarum PNU strain.