This article examines the relationship among diabetes-related stress, appraisal, coping and depressive symptoms in patients with type 2 diabetes mellitus (T2DM) using the transactional model of stress and coping (TMSC) as the theoretical framework. In this cross-sectional study, a convenience sample of 201 patients with T2DM was recruited from three outpatient clinics. Patients with depressive symptoms reported significantly more diabetes-related stress than patients without depressive symptoms. The results of path analysis suggest that patients who experience greater diabetes-related stress or greater depressive symptoms have a negative appraisal of their diabetes. Negative appraisal is, in turn, associated with greater use of avoidance, passive resignation and diabetes integration coping and lesser use of problem-focused coping. Avoidance, passive resignation and diabetes integration coping are, in turn, related to greater depressive symptoms or greater diabetes-related stress. Overall, the results of this study support the TMSC as a framework to elucidate the relationships among diabetes-related stress, appraisal, coping and depressive symptoms in patients with T2DM. However, given the cross-sectional nature of the study, we are unable to elucidate the directionality of the relationship between stress and depressive symptoms. Implications of the findings and the need for longitudinal studies to evaluate these relationships are discussed. Copyright © 2011 John Wiley & Sons, Ltd.