Benzo[a]pyrene (B[a]p) is regarded as a polycyclic aromatic hydrocarbon that results due to partial combustion of organic materials. B[a]p has variable probable toxic health effects on humans and that makes it an issue of concern to the public health. Spirulina Platensis is a type of cyanobacteria that is multicellular and filamentous, and it has gained considerable popularity in the field of medicine. Aim: This investigation was done to assess the potential protection by Spirulina against toxic effects of B[a]p in rats' heart tissues. Methods: Fifty adult male albino rats have been categorized into 5 equal groups; Negative control, Positive control (10 mL/kg corn oil), Spirulina Platensis (300 mg/kg), Benzo[a]pyrene (50 mg/kg), and Benzo[a]pyrene + Spirulina Platensis groups. All treatments were given twice per week. After four weeks, 24 hours from the last dose, rats had been sacrificed, and the oxidative-related markers; NADPH oxidase-2 (NOX-2), malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD), along with cytokines of inflammation; tumor necrosis factor-alfa (TNF-α) and interleukin-6 (IL-6) were measured in the heart. Determination of cardiac Toll-like receptor 4 (TLR4) by real-time polymerase chain reaction (RT-PCR) was also done. The left ventricular cardiac tissues were stained by both hematoxylin and eosin and Mallory trichrome stains, and the immunohistochemical expression of Connexin 43 (Cx43) was evaluated as well. Results: In the rats that were treated by B[a]p, there was an elevation in oxidative and inflammatory markers, and increased expression of cardiac TLR4. Co-administration of Spirulina with B[a]p mitigated all the measured parameters. Histopathology and immunohistochemical staining showed that the B[a]p developed histological damage and immunohistochemical changes in the left ventricular tissues and these changes were alleviated by Spirulina co-administration. Conclusion: Administration of Spirulina produced positive impact on oxidative and inflammatory markers of the heart, along with ameliorating the histopathological and immunohistochemical findings induced by B[a]p. Recommendations: Spirulina Platensis is a suggested agent for protection against cardiotoxic effects of B[a]p. Also, more studies are required to investigate cardio-protective potential as well as safe and effective doses in humans. Keywords: Spirulina, Benzo[a]pyrene, Cardiac toxicity, Rats