Cadmium (Cd) is a heavy metal in the environment and contaminated food causes a serious risk to biodiversity and human health. Cd affects Cell proliferation, differentiation, and apoptotic pathway. A growing attention is now towards the severely damaging effects of Cd and its relation to different cancers. Unfortunately, few reports found about Cd effects on salivary tissues. In our study, we will investigate the effect of Cd on Rats major salivary glands and the level of Caspase 3 in their blood. Fourteen albino Rats were allotted randomly into 2 equal groups, control group I and group II which received Cd orally by gavage needle for 24 days. Parotid and submandibular salivary glands were carefully dissected and blood samples were collected from Rats. Paraffin blocks of the salivary glands were prepared and stained with Haematoxyline and Eosin (H&E) stain, examined by light microscope examination. Caspase 3 levels were measured in the sera of Rats by enzyme immunoassay (EIA) using Rat Caspase 3 ELISA kit. Cd treated group revealed especially in the parotid glands more than submandibular glands a sever hydropic degeneration with areas of necrosis containing apoptotic cells (cellular toxicity). The serous acini appeared with loss of its acinar outlines, multiple intracellular vacuoles with compressed pyknotic nuclei. Additionally, few signs of cellular atypia appear. Our ELISA test results of Caspase 3 confirmed the apoptosis induction in Cd treated group with a high significant difference among the control group. In conclusion, our results revealed that Cd induces apoptosis and cellular toxicity in Rats major salivary tissues indicating that exposure to Cd in the environment and food is quite harmful. Our results shed a light on Cd which can be used with other heavy metal complexes as an antitumor drug in an optimized dosage.