AbstractAnxiety and depression are commonly found in patients with diabetes, but little is known about how the anxiety and depression symptoms of diabetes patients and the health-related quality of life (HRQoL) over time influence each other. Therefore, we conducted a survey among patients with diabetes (T1) and repeated the survey after 3 months (T2). Linear regression models and cross-lagged structural equation models were used to analyze the associations between anxiety and depression symptoms and HRQoL within and across time intervals. Correcting for baseline index and potential confounders, the HRQoL index at T2 reflected the change in anxiety/depression between T1 and T2 more than anxiety/depression at T1 (P < 0.05). Similarly, anxiety and depression at T2 reflected the change in the EQ-5D index over time more than the index at baseline (P < 0.05). Our longitudinal data fitted well in a cross-lagged model with bi-directional pathways of associations between anxiety and HRQoL, as well as depression and HRQoL, among adult patients with diabetes (x²/df = 1.102, P = 0.256; CFI = 1.000, RMSEA = 0.030). Our findings support early detection of anxiety and depression, as well as comprehensive efforts improving HRQoL for patients with diabetes.