Somatostatin (SRIF) influences the release of two important neuromodulators of retinal circuitry, dopamine (DA) and nitric oxide (NO). The aim of the present study was to examine whether DA and NO modulate SRIF release in rat retina, and the mechanisms involved in their actions. Retinas of adult female Sprague–Dawley rats (250–300g) were mechanically detached from the eyecup and ex vivo experiments were performed. Retinal explants were incubated in the presence of dopaminergic [DA (10μM, 100μM and 200μM), apomorphine (nonselective D1/D2 agonist, 0.50μM, 1.0μM and 10μM), A68930 (D1 selective agonist, 0.50μM, 1.0μM and 10μM), quinpirole (D2 selective agonist, 0.50μM, 1.0μM and 10μM), SCH 23390 (D1 selective antagonist, 250nM and 500nM) and sulpiride (D2 selective antagonist, 100μM and 200μM)], and nitrinergic agents [arginine (62.5μM–5mM), SIN-1 (50μM, 100μM and 500μM) and 8-Br-cGMP (50μM, 250μM and 500μM)]. SRIF levels were quantified using radioimmunoassay (RIA). Dopamine had no effect on SRIF levels. Apomorphine produced a concentration dependent decrease and increase in SRIF levels, suggestive of pre- and postsynaptic effects. A68930 (10μM) and SCH 23390 (250nM and 500nM) mimicked and reversed apomorphine's postsynaptic actions, respectively. Quinpirole had no effect, but blockade of D2 autoreceptors by sulpiride (200μM) afforded an increase in SRIF levels. Arginine and SIN-1 increased, and 8-Br-cGMP attenuated SRIF levels. These results show that dopamine D1 receptors, and NO/peroxynitrite agents modulate SRIF release in the retina suggesting that the triad SRIF–DA–NO have reciprocal interactions via which they regulate retinal circuitry and vision transduction.