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High somatic cell counts (SCCs) in milk significantly influence the quality of milk and give rise to substantial economic loss. The present study was aimed to investigate the effect of extreme heat and cold compared to other season and melatonin (MLT) on milk SCCs in Chinese crossbred (Nili-Ravi×Murrah) buffaloes. We collected the 1948 milk SCCs data records from 2012 to 2017 to explore the effect of different month in China on milk SCCs. Meanwhile, twenty buffaloes with relatively high milk SCCs were employed and randomly divided into two groups (T1 and T2, n=10 each group) to evaluate the effect of MLT treatment on milk SCCs, blood antioxidant activities and immune levels of buffaloes during summer in China. Results showed that the milk SCCs in high temperature seasons (July and August) and low temperature seasons (December, January and February) were significantly higher compared with other months (P<0.05). In summer, MLT treatment significantly reduced milk SCCs and increased the IgM and superoxide dismutase (SOD) levels in plasma on day 1 after MLT treatment, and then both IgM and SOD levels were decreased significantly. In conclusion, our study demonstrated that environmental temperature stress (heat and cold) caused the higher milk SCCs and MLT treatment improved the quality of milk by reducing SCCs suggesting that MLT could improve immune activity in buffaloes. [ABSTRACT FROM AUTHOR]