This study aimed to evaluate the effects of dietary egg yolk phosphatidylcholine (EPC) and soybean phosphatidylcholine (SPC) on obesity mice fed a high-fat diet (HFD). After 60 days of dietary intervention, the effects were evaluated by biochemical indices and serum lipidomic analysis. EPC and SPC markedly reduced serum total cholesterol, serum triacylglycerol (TAG) and low-density lipoprotein cholesterol, while increased high-density lipoprotein cholesterol. EPC was more effective in reducing malondialdehyde and superoxide dismutase in liver than SPC. Main lipids including glycerophospholipids, TAG, sphingolipids and fatty acyls were significantly modified by EPC. Compared with HFD, EPC increased 10 main differential lipids such as phosphatidyl ethanolamine (22:6_20:0). The expressions of related protein including sterol-regulatory element binding proteins sterol-regulatory element binding proteins (SREBP-1c) and peroxisome proliferator-activated receptor α (PPAR-α) were significantly down-regulated with EPC treatment. Therefore, EPC was more effective than SPC in improving obesity by regulating glycerophospholipid metabolism.