Objective To investigate the effect of protein kinase MPK-1 on lipid metabolism, and explore the underlying mechanism. Methods C.elegans was served as model organism, and the expression of mpk-1, sbp-1 and daf-2 genes was interfered with RNA interference (RNAi). The fat contents in C.elegans were observed by Oil-red O staining and Sudan black staining, and were quantified after washing off the dye. Then, the mechanism of effect of MPK-1 on fat accumulation was determined by the combination of RNAi knockdown technique and the green fluorescence change in a specified location. Results The fat content significantly increased after interference of mpk-1 gene expression. Fluorescence microscopy revealed that fluorescence enhancement was detected after interference of mpk-1 gene expression in C.elegans with expression of lipogenic enzymes fat-7∷gfp, and intranuclear transference of DAF-16 was promoted after interference of mpk-1 gene expression in C.elegans with expression of DAF-16 fluorescin regulating fat-7. Conclusion Protein kinase MPK-1 may inhibit FAT-7 activity through DAF-16, and reduce the fat accumulation.