The purpose of this research was to determine the effect of chronic stress on the structure of the rat submandibular salivary gland and the involvement of a nanolycopene emulsion in mitigating this effect. In this research, forty adult male albino rats were divided into four equal groups: group 1 (control group), group 2 (nanolycopene group), group 3 (stress group) and group 4 (stress+ nanolycopene group). The experiment continued for 4 weeks. Serum corticosterone level was assessed at the end of the experiment and submandibular salivary glands were processed for histological, ultrastructural study and immunohistochemical analysis of proliferating cell nuclear antigen. The results showed that rats exposed to chronic stress exhibited significant increase in serum corticosterone level. Histological and ultrastructural examination of their submandibular salivary glands revealed many signs of degeneration with marked intracellular changes in the cytoplasmic and nuclear structure of the acinar and ductal cells. Besides, the glands showed significant reduction in proliferating cell nuclear antigen immunoexpression. Interestingly, intake of nanolycopene emulsion during chronic stress abolished stress elevating effect on serum corticosterone level. The submandibular salivary glands regained its almost normal architecture and the proliferating cell nuclear antigen expression simulated the control group. Conclusion: Exposure to chronic stress caused deleterious effects on rats' submandibular salivary glands. However, nanolycopene emulsion was able to ameliorate chronic stress effects. Hence, it is highly recommended to use nanolycopene emulsion daily for individuals subjected to chronic stressful life.