Objective To rescue homozygous (LO) lipoprotein lipase (LPL) knockout mice that should have died in 48 hours after birth by somatic gene transfer using a beneficial mutant of LPL gene (LPL447). Method A recombinant adenoviral vector expressing LPL447 was delivered to the neonatal mice by intramuscular route. The phenotypes of rescued mice were analyzed. Results 75% of LO mice survived the entire suckling period and lived for up to normal adulthood, which is greatly higher than the survival rate achieved by other groups abroad using wild type LPL gene. Adult LO mice exhibited extremely high triglyceride levels.Conclusion Adenovirus mediated LPL447 gene transfer during neonatal stage can rescue the LO mice successfully. Adult LO mice can be used as a severe hyperlipemia animal model for further investigation.