Insulin resistance is a key factor in the etiology of type 2 diabetesmellitus. Genes involved in insulin resistance are therefore likely to affectsusceptibility to these diseases. One such gene, PC-1, encodes plasmacell glycoprotein-1 which may play an essential role in insulin resistanceby inhibiting insulin receptor signaling through interaction with the αsubunit The PC-1 K121Q polymorphism is associated with type 2diabetes mellitus and obesity. The effect of PC-1 K121Q genepolymorphisms on susceptibility to type 2 diabetes mellitus has beeninvestigated extensively. Several findings on positive disease associationshave been observed. To examine the association of PC-1 K121Qpolymorphisms and susceptibility to type 2 diabetes mellitus in Egyptianpopulation a study of 40 individuals with type 2 diabetes mellitus and 20control subjects was done. PC-1 K121Q genotyping was performedusing PCR followed by digestion with Ava II restriction enzymes. Datawere analyzed using X2 - test. A significant difference in PC-1 K121Qgenotype frequencies between cases (92.5%) and controls (70) (P< 0.05)was found. Conclusion: The findings of the study suggest that the PC-1K121Q polymorphism may influence genetic susceptibility to T2DMamong the Egyptians.