Background: The prevalence of Type 2 diabetes is increasing steadily at an alarming rate and Ethiopia is placed fourth among the top five countries of the Africa region according to the International diabetes federation. Regardless of its burden, the self-care behaviors are still unknown. This study is aimed to determine the level of diabetes self-care practice and factors associated with among Type 2 diabetes mellitus patients in public hospitals of Tigray region.Methods: Institution-based, cross-sectional study was conducted in six selected hospitals of Tigray region from January to February, 2020. Data was collected by trained nurses with a face to face interview method using Summary Diabetes Self-Care Activities (SDSCA). Bivariate and multivariate logistic regression was used to identify factors associated with self-care practices. Statistical significance was declared at P-value < 0.05.Results: A total of 570 patients with type 2 diabetes were included in this study. The mean age of the participant was 46 ± 14.6 years. Less than half (46.7%) of the participants has good diabetes self-care practices. Urban residency (AOR=2.79, 95% CI 1.858-4.205), age group above 64 years (AOR=2.384, 95% CI 1.258-4.518), not having formal education (AOR=2.616, 95% CI 1.337-4.518), having family or social support (AOR=1.878, 95% CI 1.243-2.837), duration DM above 10 years (AOR=2.325, 95% CI 1.224-4.418), having personal glucometer at home (AOR=5.9, 95% CI 2.790-12.764) were determinant factors of good diabetes self-care practice. Conclusion: the diabetes self-care practices in the region was found to be low. Health care providers might have to consider actions to act on the identified factors and improve self-care practices of the patients. Especially, focusing on caring and giving follow up services to younger adults and DM patients coming from a rural areas.