Lead acetate (Pb) is an oldest and widespread environmental toxicant that led to cumulative injury in humans and all living organisms through induction of oxidative stress. Spirulina platensis (SP) is a cyanobacteria with strong antioxidant, anti-inflammatory, and immune stimulatory effects. In this study, the ameliorative effect of SP was evaluated against the dietary sub chronic lead toxicities in rabbits. A total number of 75 male New Zealand rabbits were allocated randomly into 5 groups; the first group feed on basal diet alone and served as control group, the second group feed on basal diet + 100 mg Pb /kg diet, the third, fourth, and the fifth groups feed on basal diet + 100 mg Pb /kg diet + SP (0.5, 1, or 1.5 g/kg diet; respectively), the experiment was extended for 8 weeks. Results revealed a significant improvement in some of growth parameters like final body weight and daily weight gain, blood parameters in rabbits treated with SP at level 1.5 g/kg diet followed by those receiving SP 1 g/kg diet. However, a significant decrease in blood parameters, liver function, renal parameters, lipid profiles, oxidative parameters (malondialdehyde and protein carbonyl), heart indices (creatine phosphokinase, creatine kinase-muscle/brain, lactate dehydrogenase), total Pb residues in muscles, and area percent of nuclear factor kappa b immune expression were reported in groups supplemented with different levels of SP. Pathologic analysis of liver, kidneys, and heart revealed moderate to severe degenerative and necrotic changes in Pb- exposed rabbits, which is ameliorated with supplementation of SP in different levels. Conclusively, dietary supplementation of SP at different levels attenuated the cumulative effect of lead in rabbits in dose-dependent manner; this attenuation may be attributed to its anti-oxidative, anti-inflammatory, as well as its immune stimulant effect.