Diabetic Retinopathy is a common complication of diabetes, stems from intricate molecular interactions. It is characterized by progressive damage to the microvasculature of the retina, and ultimately leads to vision impairment and blindness. A total of 48 female Sprague-Dawley (SD) rats were divided into four groups as follows: the Normal Control (NC) group (n=12), the High-Fat High-Sugar (HFHS) group (n=12), the HFHS + Streptozotocin (STZ) group (n=12), and the HFHS + Metformin (MR) group (n=12). The TGF-β1 and MMP-9 expressions in lens epithelial cells (LECs) were assessed at two-time points post-modeling (week 1 and week 2). We extracted the tissue sections, mounted using coverslips and observed under the microscope to investigate the follicle of the tear duct associated lymphoid tissue (TALT). Statistical analyses, including correlation tests, were performed using GraphPad software. Our results showed that the MMP-9 expression significantly increased from week 1 to week 2 in the HFHS+STZ, HFHS+MR, and HFHS groups (p<0.001), indicative of potential kidney complications related to diabetes. Conversely, the control group (NC) maintained stable MMP-9 levels. Regarding TGF-β1, the HFHS+STZ group exhibited a significant increase from week 1 to week 2 (p<0.001), while the NC group remained stable (p<0.001). Similar trends were observed in the HFHS+MR and HFHS groups, indicating rising TGF-β1 levels over time. Immunostaining of TALT showed brown B-cell aggregates and TALT lymphocytes in the Harderian glands. In conclusion, our findings highlight the complex interplay between TGF-β1 and MMP-9 in diabetic retinopathy.