Trace metals are naturally materials found in water, earth crust and rocks, making the exposure rate to these metals is high affecting vital organs of the body. Diabetes is an endocrinal disease that can also affect many body organs by its oxidative stress like action. The present study was conducted to examine the effect of various trace metals on some parenchymatous organs in a diabetic and non-diabetic rat model. 120 Albino Wistar rats were used, and diabetes was induced in 60 rats. All rats were divided into twelve groups. All of them received trace metals for 4 weeks, except the control groups. At the end of the study, samples from blood (for biochemical analysis), heart, pancreas, liver, kidney and spleen (for histopathological and gene expression analysis) were collected. All trace-metal-treated groups showed histopathological insult and functional disability. The extent of injury was extensive in diabetic groups if compared to non-diabetic groups. The genetic expression analysis showed increase in apoptotic genes CASP-3 and a marked decrease of anti-apoptotic genes BCL-2. The present study showed that trace metals are highly toxic to various organs of the body even in low concentration. The diabetic rats are more susceptible to trace-metal-induced cellular damage through gene-mediated pathway. CASP-3 gene plays an important role in trace-metal-associated tissue injury. The present study showed that cadmium affects mainly hepatic and splenic tissues. Chromium, arsenic and thallium affect mainly the kidney, heart and pancreas respectively.