Objective To explore the influence of hsa_circ_0004535 on type 2 diabetes(T2DM) combined with metabolic-associated fatty liver disease(MAFLD) model mice. Methods From September 2021 to March 2022. Forty-eight healthy Balb/c mice of SPF grade were selected for modeling and grouping, control group, Each group had 6 mice.Control group: normal feed; T2DM group: diabetes model induced by high glucose diet; T2DM combined MAFLD group: high fat and high glucose feed was given at the same time to induce diabetes combined with fatty liver model; T2DM combined MAFLD + hsa_circ_NC group: after 4 weeks of modeling, 10 nmol/only hsa_circ_NC was injected into the tail vein; T2DM combined MAFLD +hsa_circ_0004535 group: after 4 weeks of modeling, 10nmol/only circ_0004535 was injected into the tail vein; T2DM combined MAFLD+miRNA_NC group: after 4 weeks of modeling, 10nmol/only miRNA blank control was injected into the tail vein; T2DM combined MAFLD+miR- 1827agomir group: after 4 weeks of modeling, 10nmol/only miR-1827agomir was injected into the tail vein; T2DM combined MAFLD+miR-1827antagomir group: after 4 weeks of modeling, 10nmol/only miR-1827antagomir was injected into the tail vein; after the interventions, body weight was measured and recorded weekly. Glucose tolerance and insulin tolerance tests were performed; blood lipids and liver function were measured; liver index and insulin resistance index were calculated; and pathological index tests (HE and oil red O staining, immunohistochemistry, TUNEL staining, Masson staining) were performed to measure the degree of hepatic inflammation, fat deposition and fibrosis. Results (1) The body weight, liver weight, liver index, insulin resistance index and biochemical indexes of the animals in the hsa_circ_0004535 injection group were significantly lower than those in the hsa_circ_NC injection group and the T2DM combined MAFLD group (both P < 0.05). (2) HE staining showed that in the T2DM combined MAFLD+ circ_0004535 group, the steatosis vacuoles were reduced and smaller, and the inflammatory cell infiltration was reduced. The results of oil red staining were consistent with those of HE staining. (3) TUNEL staining showed that TUNEL-positive cells were significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group (P < 0.05). (4) Masson staining showed that collagen fiber deposition was significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group (P < 0.05).Conclusion The expression of hsa_circ_0004535 and miRNA-1827 plays an important role in regulating lipid metabolism, insulin sensitivity, inflammatory pathways, hepatocyte apoptosis, and hepatic fibrosis-related pathways in the animal model of T2DM combined with MAFLD.