To investigate the preventive and therapeutic effects of artesunate (ART) on splenic fibrosis in type 2 diabetes mellitus (T2DM) rats,and to reveal its related molecular mechanisms,providing a experimental basis for the prevention and treatment of splenic injury in T2DM.Fifty SD rats were randomly divided into control group and model group.After eight-week high glucose and high fat feeding in the model group,streptozotocin was injected to make a T2DM model,and then they were randomly divided into diabetes group,metformin intervention group,artesunate intervention group,metformin and artesunate intervention group.After four-week treatment,the spleen tissues of rats were harvested.The spleen was weighed;HE,Masson staining were used to observe the pathological changes of the spleen;Immunohistochemistry,Western blot were used to detect the expression of transforming growth factor-β (TGF-β1),SMAD family member 2(Smad2),SMAD family member 7(Smad7),and type I collagen in the spleen tissues;And qRT-PCR was used to detect the mRNA levels of TGF-β1,Smad2,Smad7,and collagen I in the spleen tissues.The spleen index decreased.The structure of spleen was damaged and disorganized.Compared with control group,there were fibrosis and hyperplasia in spleen observed in diabetes group.Compared with the diabetes group,the spleen injury and fibrosis were attenuated in drug intervention group.The expression and mRNA contents of TGF-β1,Smad2,and collagen I in the spleen tissues significantly decreased.The expression and mRNA content of Smad7 significantly increased.ART ameliorated splenic injury and inhibited splenic fibrosis in T2DM rats,and the mechanism of action may be related to the inhibition of TGF-β/Smad signaling pathway.