cAMP-dependent protein kinase A (PKAc1) plays a critical role as a negative regulator of egress by rapidly suppressing calcium signaling after invasion. The activity of protein kinase A (PKAc1) is governed by adenylate cyclases and phosphodiesterases that serve to produce and hydrolyze cAMP, respectively. Herein, we investigated the phosphodiesterase PDE2, which one of two essential isoforms out of a total 18 PDE genes in T. gondii. Immunoprecipitated PDE2 preferentially hydrolyzed cAMP in vitro and knockdown of PDE2 led to elevated levels of cytosolic cAMP in vivo, consistent with its role as a cAMP-specific PDE. Knockdown of PKAc1 also resulted in higher cytosolic cAMP levels suggesting that PKAc1 is likely required for PDE2 activation and cAMP turnover. PKAc1 phosphorylation of PDE2 was confirmed in vitro and differentially phosphorylated residues were identified using a conditional PKAc1 knockdown line expressing epitope tagged PDE2. Phospho-mimetic and -ablative forms of PDE2 were purified and tested for activity. Select phospho-mimetic mutations in PDE2 retained activity whereas the corresponding phospho-ablative mutations lost activity, confirming that PKAc1 phosphorylation activates PDE2, while dephosphorylation inhibits activity. Finally, to examine the impact of PDE2 on PKAc1 function, PDE2 depleted parasites were stimulated with zaprinast or ionomycin and then assessed for egress. Zaprinast, but not ionomycin, failed to induce Ca2+ mobilization and egress in PDE2 depleted parasites. These defects were partially rescued when PKAc1 was inhibited by H89 confirming that PKAc1 is primarily responsible inhibiting egress. These data support a model in which PKAc1 targets a process downstream of cGMP and upstream of Ca2+ release to prevent egress, and this block is relieved when PKAc1 phosphorylates PDE2 leading to consumption of cAMP and inhibition of PKAc1. The resulting negative feedback loop counteracts the PKG pathway that drives motility, invasion and egress, thus allowing equilibrium conditions during intracellular development.