Objective: Peroxisome proliferator-activated receptor gamma (PPAR gamma), lipids, lipoproteins, and adipokines have recently been shown to be associated with psychiatric diseases. Our major aim is to investigate the contribution of the PPAR gamma gene polymorphism, adipokines, lipids, and lipoproteins to the development of major depression. Material and Methods: The frequency of Pro12Ala in exon 2 and C478T in exon 6 of the PPAR gamma gene, lipids and adipokines in major depression (n = 78) and control subjects (n = 64) were analyzed. Genotypes of PPAR gamma gene polymorphisms were examined. Serum leptin, adiponectin, and resistin were studied by enzyme-linked immunosorbent assay (ELISA). Serum apo A1, apo B, and Lp(a) levels were determined by immunonephelometry. Serum total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol levels were analyzed by enzymatic methods. Results: The genotypes of exon 2 and exon 6 distribution did not differ between the control subjects and patients with major depression. Frequencies of genotypes of Pro12Ala, and Ala12Ala in exon 2 in overweight and obese patients with major depression were higher than those of overweight and obese controls. C478T polymorphism was highest in overweight and obese patients with major depression. Pro12Ala and Ala12Ala genotypes in exon 2 of PPAR gamma gene in patients were found to be associated with triglyceride and HDL-cholesterol. There were significant differences regarding glucose, total cholesterol, LDL-cholesterol, apo B, Lp(a), adiponectin and resistin levels between patient and control subjects. Conclusion: PPAR gamma exon gene polymorphisms, alterations in lipid profile and adipokines may be associated with the development of major depression.