Background: Indoxyl sulfate is considered to play a pathological role in the progression of chronic kidney disease. The aim of this study was to investigate the deleterious effects of indoxyl sulfate on kidney mesangial cells. Materials and Methods: Rat renal mesangial cells were exposed to indoxyl sulfate at a serial concentrations. Cytotoxicity of indoxyl sulfate on renal mesangial cells was determined using MTT assay. Protein levels of cleaved caspase-3, angiotensin, angiotensin converting enzyme (ACE) and renin were detected by immunoblotting. Reverse transcriptional PCR was performed to determine the mRNA expression. Results: Level of cleaved caspase-3 was augmented while the cell viability was inhibited by indoxyl sulfate in a dose-dependent manner. The mRNA expressions of pro-renin and ACE were upregulated in mesangial cells exposed to indoxyl sulfate. Level of renin and ACE was increased in response to indoxyl sulfate exposure in time-dependent fashion. Conclusion: Indoxyl sulfate increased viability and induced cell death of renal mesangial cells, which is time-dependent. The loss of cell viability is attributed to caspase-3 activity through apoptosis pathway. RAS in renal mesangial cells is activated in response to indoxyl sulfate treatment.