Objectives: To explore whether serine can protect myocardial fibrosis as a ligand of glycine receptor (GlyR). Methods: Serine or saline were injected intraperitoneally to mice a week before angiotensin Ⅱ(Ang Ⅱ) administrated by using an osmotic pump, and the myocardial fibrotic status in mice was detected 28 days later. The expression levels of inflammatory markers in cardiomyocytes response to angiotensin Ⅱ(Ang Ⅱ) were detected with or without serine in vitro. Primary cardiac fibroblast cells were isolated from neonatal rat and treated with Ang Ⅱ or serine，respectively，and then the expression levels of collagen Ⅰ and collagen Ⅲ were checked by quantitative PCR. The expression levels of collagen Ⅰ collagen Ⅲ were checked in both cardiac fibroblasts and cardiomyocytes co-cultured system. mRNA levels of collagen I and Ⅲ were checked after GlyR knocked down by siRNA transfection in cardiomyocyte. Results: In the presence of cardiomyocyte, production of collagen Ⅰ and collagen Ⅲ was enhanced in cardiac fibroblasts after Ang Ⅱ treatment, however，the enhancement is inhibited by serine. Importantly, the protective of serine on cardiac fibrosis was abolished by GlyR knockdown. Conclusion: Serine could blunt myocardial fibrosis through GlyR in cardiomyocyte.