In the current study, we demonstrated that L13Rik mediates HG-induced MC hypertrophy and ECM accumulation by regulating the miR-2861/CDKN1B axis, as evidenced by the following: (i) L13Rik was increased in DN patients, diabetic mice, and HG-treated MCs; (ii) L13Rik depletion alleviated HG-induced MC hypertrophy and ECM accumulation; (iii) L13Rik acted as ceRNA to sponge miR-2861; (iv) MiR-2861 suppressed HG-induced MC hypertrophy and ECM accumulation; (v) MiR-2861 antagonized the effect of L13Rik on MC hypertrophy; (vi) L13Rik increased CDKN1B expression by sponging miR-2861. The gene discussed is CDKN1B; the disease is liver dysplastic nodule.