Taken together, these findings demonstrate that the inhibition of SC‐CB1R reversed the DM‐induced energy metabolic imbalance of SCs, alleviated the histopathological changes of DPN, and ameliorated neuropathic symptoms, indicating that SC‐CB1R may play a key role in DM‐induced metabolic remodeling of SCs, thus indicating it as a promising therapeutic target for DPN. This evidence concerns the gene CNR1 and diabetes mellitus.