Background: Allergic rhinitis (AR) and antihistamine usage can cause xerostomia. The study aims to examine if AR, antihistamines, and the use of antihistamines in AR have histopathological effects on the submandibular gland. The study also investigates the effect of oxidant and antioxidant plasma parameters. Methods: Thirty-two adult Sprague-Dawley rats were used in the study. The rats were divided into the 4 following groups: the control group (C group); the AR group; an antihistamine-treated group (AH group); and an AR plus antihistamine-treated group (AR+AH group). The AR and AR+AH groups were sensitized using ovalbumin. The AR+AH and AH groups received desloratadine. The histopathological effects of AR and desloratadine treatment on the submandibular glands (SMGs) and the values of the oxidative and antioxidative serum parameters were evaluated. Results: Histopathological examination of sections of the SMGs from the AR and AH groups revealed that vacuolization was present in the mucous acinar and ductal cells and that the number of connective-tissue cells was greater than that of the control group. The appearances of the AR+AH-group sections were similar to those of the control group. The superoxide dismutase activity level and the glutathione level were relatively decreased in these groups compared with those of the control group. The malondialdehyde level in the AR group was increased compared with that of the control group. Conclusion: The AR-induced pathological changes were diminished by desloratadine treatment. Thus, the new-generation antihistamine desloratadine may be used to treatment of AR patients who have xerostomia.