Microplastics (MPs) are environmental pollutants attracting widespread attention due to their environmental omnipresence and potential health effects. MPs undergo ageing in the environment and our previous research found that aged Polystyrene microplastics (PS-MPs) affected lipid metabolism in healthy female mice, but not males. In this study, we examined the effects of aged PS-MP exposure on lipid metabolism in mice with Metabolic Associated Fatty Liver Disease (MAFLD). 14 female and 14 male mice were furnished with a high-fat diet (HFD) for eight weeks to create MAFLD model mice. They were then orally administered aged PS-MPs for four weeks, and changes in the AMP-activated protein kinase signalling pathway were examined in order to determine PS-MP's effect on hepatic metabolism. The outcomes showed that though serum estradiol, inflammatory gene expression and ROS levels increased significantly in both male and female HFD-aged PS-MP groups, hepatic steatosis was attenuated only in the female group. Furthermore, serum ERα, ERβ, AMPKα, acetyl-CoA carboxylase, sterol regulatory element binding protein-1c, and Fas expressions were significantly increased in the MAFLD mice groups compared to the control group. Combining serum E2 levels, AMPK pathway changes, oxidative stress markers, and inflammatory gene levels, aged PS-MPs may stimulate E2 production and mobilize the liver AMPK signalling pathway of both male and female MAFLD mice. However, lipid metabolism is only affected in female MAFLD mice, suggesting other possible mechanisms besides the AMPK pathway may be at play. These results provide a new perspective on the potential health effects of MP exposure in individuals with metabolic disorders such as MAFLD.