Objective: Present study aims to evaluate oxidative stress-mediated toxicity mechanisms of nano-ZnO (N-ZnO) compared to ZnCl2 and bulk-ZnO (M-ZnO), using cyanobacterium as a toxicity assessment tool. Methods: Nostoc muscorum was used as a test organism and the experiments were performed in parallels after treated with 2-128 mu M of N-ZnO, M-ZnO, and ZnCl2. Results: Low concentrations of ZnCl2 (2-8 mu M) and N-ZnO (16-32 mu M) led to a significant increase in the carotenoids, which could be ascribed to its role as an antioxidant, whereas higher concentrations were inhibitory to the photosynthetic pigments. Enhanced activities of superoxide dismutase (SOD), peroxidase (POD) and accelerated lipid peroxidation depicted significant accumulation of superoxide and peroxide radicals in N. muscorum exposed to N-ZnO and ZnCl2. The non-enzymatic antioxidants such as proline and total phenols also showed enhanced accumulations up to 16 and 64 mu M of ZnCl2 and N-ZnO treatment, respectively. Conclusion: Our results for the very first time depicted the significant accumulation of stress biomarkers in N. muscorum in response to deleterious effects of oxidative stress caused by N-ZnO, ZnCl2, and M-ZnO. Present results revealed varying levels of toxicity of various forms of zinc, which decreased in an order of ZnCl2 > N-ZnO > M-ZnO.