Retinitis pigmentosa (RP) is an inherited and untreatable retinal dystrophy that leads to blindness at an early age. Cyclic guanosine monophosphate analogue, 8- bromo- β- phenyl- 1, N²- ethenoguanosine- 3′, 5′- cyclic monophosphorothioate Rp- isomer (CN03), has shown preclinical promise as systemic treatment in an RP mouse model. We explored intravitreal (IVT) CN03 delivery and resulting biochemical responses in rabbits. To prolong activity, we used poorly water-soluble benethamine (BNE) and benzathine (BNZ) salts to sustain CN03 release. Crystallinity, particle size, and solubility of CN03-BNE (385.4 ± 37.07 µM) and CN03-BNZ (275.9 ± 9.24 µM) in vitreous humor were determined. Suspension of 15% CN03-BNZ showed dissolution half-life of 7.40 ± 0.86 days in vitro and CN03 release of one month after IVT injection in rabbits . Ex vivo in retina lysates, CN03 showed concentration-dependent inhibition of PKG kinases. Furthermore, downregulation of PKG-related kinases and RP-linked cellular pathways (e.g., calmodulin, PI3K-AKT-mTOR, and NF-κB) in rabbit retina and peripheral blood monocytes (PBMC) were seen after IVT injection of CN03-BNZ suspension. Kinase inhibition profiles in the retina and PBMCs overlapped, but plasma CN03 levels were much lower than in the retina. PBMC kinase activity is a potential biomarker for retinal kinase inhibition, warranting further studies in disease state models. Overall, intravitreal delivery of cGMP analogue CN03 as a poorly water-soluble salt demonstrates kinase inhibition and sustained ocular delivery. These results lay the foundation for further translational studies towards intravitreal treatment of the RP with cGMP analogues.