Abstract: We have previously demonstrated leporine platelets lack imidazoline (I)1 receptors and effects of imidazoline α2-adrenergic agents on platelet aggregation differ in dogs and rabbits. In order to compare the effects of various α-adrenergic agents on canine and leporine intraplatelet cAMP ([cAMP]i) and thromboxane B2 ([TXB2]i), elevations of both forskolin-induced [cAMP]i and adrenaline-collagen-induced [TXB2]i were determined using immunoassay. The α2-adrenoceptor antagonists were ineffective in canine platelets, but the α2-adrenoceptor agonists adrenaline inhibited forskolin-induced increase in [cAMP]i. Adrenaline was ineffective in leporine platelets, but α2-adrenoceptor antagonists were effective on forskolin-induced increase in [cAMP]i. Adrenaline-collagen-induced elevation of [TXB2]i in canine platelets was not inhibited by the non-imidazoline α2-adrenoceptor agonist xylazine, but was inhibited by α2-adrenoceptor antagonists, an imidazoline α2-adrenoceptor agonist (naphazoline) and an imidazoline compound (antazoline). In contrast, α2-adrenoceptor agonists were ineffective on [TXB2]i in leporine platelet-rich plasma and all drugs were ineffective on [TXB2]i in leporine washed platelets, demonstrating various imidazoline or nonimidazoline α2-adrenergic agents effectively inhibited forskolin-induced elevation of [cAMP]i and adrenaline–collagen-induced [TXB2]i and the effective drugs differed between dogs and rabbits. We propose imidazoline α2-adrenergic agents suppress cAMP production via the α2-adrenoceptor while exerting a negative control on TXB2 generation via the arachidonic acid-thromboxane A2 pathway.