The aim of the present study was to assess the systemic effect of thymoquinone (TQ) on bone healing by starting TQ administration, either 40 days before, or on the day of the surgical procedure and continuing during the healing period of 28 days. Eighteen experimental rats were divided into three groups and defects were created in their tibias. The following procedures were performed for each group: Control group (C): No systemic drug administration (n D 6); Test group 1 (T1): Systemic TQ was administered daily starting 40 days before creation of the defect and additionally during the post-operative healing period of 28 days (n = 6); Test group 2 (T2): Systemic TQ was administered daily after creation of the defect and during the healing period of 28 days (n = 6). Quantitative measurement for new bone formation, osteoblast lining and semi-quantitative measurement of capillary intensities were examined and statistically analysed. There was a significant increase in the ratio of new bone per total defect area and new bone trabeculae lined by active osteoblasts in both test groups (T1 and T2) compared to control group (p < 0.05). However the difference between T1 and T2 was not statistically significant. TQ-administered groups also showed an increase in capillary intensity in the defect area compared to the control group (p < 0.05). Systemic administration of TQ either starting 40 days before or on the day of surgery accelerated new bone formation in a rat model and can be advocated as an adjunct to expedite bone healing.