Introduction: Risk factors for type 2 diabetes mellitus (T2DM) include obesity and some genetic factors. Obesity involves mild chronic inflammation that predisposes cells to insulin resistance. Two genes that influence obesity and insulin resistance are Proconvertase-1 (PC-1) and resistin (RETN). PC-1 affects the activation of hormones that regulate satiety and hunger. Resistin is one of the inflammatory factors that influence the occurrence of insulin resistance. This study aimed to determine the influence of polymorphism in the PC-1 gene rs1044498 (C>A) and resistin gene RETN + 299 G>A rs3745367 on the risk of diabetes in obese Papua population. Methods: This study involved 58 obese people with T2DM and 58 obese people without DM. We examined the characteristics of blood pressure, lipid profile and insulin resistance by HOMA-IR. The genes examined were PC-1 rs1044498 (C>A) and RETN+ 299 G>A rs3745367 by the PCR-RFLP method. The relationship of gene variations with biochemical parameters was determined with analysis of variance. The results were considered significantly different if P < 0.05. Results: In this study, parameters of diastolic blood pressure, triglycerides and insulin resistance were higher while high density lipoprotein (HDL) levels were lower and significantly different in the obese with T2DM group compared to the obese only group. The carrier of the A allele in the PC-1 gene rs1044498 was higher in the obese group than the obese with T2DM but not significantly different in biochemical parameters. Carrier of the AA genotype in the RETN gene + 299 G>A rs3745367 had higher triglycerides and HOMA-IR and lower HDL levels significantly different (P<0.05) than other genotypes in the obesity with T2DM group. Conclusion: PC-1 rs1044498 gene was a risk factor for obesity but not for T2DM, while RETN gene rs3745367 was a risk factor for dyslipidemia and diabetes in obese people in the Papua population.