Abstract: Background and Objective: Hypercoagulability, inflammation, cardiovascular problems and stroke are common complications of haemoglobinopathies and a leading cause for hospital admission among patients. The influence of a polyherbal formula on endothelial dysfunction, coagulation indices and inflammation was investigated in 2-butoxyethanol-induced experimental model of haemoglobinopathy in adult rabbits. Materials and Methods: A total number of 20 healthy rabbits were randomly selected for this study and divided into groups. Twelve rabbits were administered 2.5 mL kg–1 of 2-butoxyethanol per os (p.o) and 1 mL kg–1 of 100 mg mL–1 polyherbal formula for 15 days, respectively pre- and post-2-butoxyethanol administration while the remaining six (6) were grouped as non-exposed/control. The levels of coagulation indices, inflammation marker and platelets were then evaluated. Tissue histology was used to assess the expression of microvascular occlusion and ischaemia. Results: Polyherbal formulation treatment significantly (p<0.05) reduced circulating C-reactive protein level as well as the platelet dyscrasias and associated endothelial dysfunction by reducing the levels of coagulation indices. There was also down-regulation of the expression of tissue necrosis in the liver and spleen of rabbits treated with 2-butoxyethanol as a result of Polyherbal treatment. Conclusion: Polyherbal formulation was found not to have any metabolic toxicity and was able to prevent 2-butoxyethanol-induced hypercoagulability and circulating thrombose as well as endothelial and inflammatory perturbation in rabbits when administered for 15 days before and after exposure to the 2-butoxyethanol induced haemoglobinopathy complications.