The objective of this study was to investigate the influence of the genesencoding the KIRreceptors and their HLAligands in the susceptibility of oculartoxoplasmosis. A total of 297 patients serologically-diagnosed with toxoplasmosis were selected and stratified according to the presence (n = 148) or absence (n = 149) of ocular scars/lesions due to toxoplasmosis. The group of patients with scars/lesions was further subdivided into two groups according to the type of ocular manifestation observed: primary (n = 120) or recurrent (n = 28). Genotyping was performed by PCR-SSOP. Statistical analyses were conducted using the Chi-square test, and odds ratio with a 95% confidence interval was also calculated to evaluate the risk association. The activating KIR3DS1 gene was associated with increased susceptibility for oculartoxoplasmosis. The activating KIR together with their HLAligands (KIR3DS1-Bw4-80Ile and KIR2DS1+/C2++ KIR3DS1+/Bw4-80Ile+) were associated with increased susceptibility for oculartoxoplasmosis and its clinical manifestations. KIR-HLA inhibitory pairs -KIR2DL3/2DL3-C1/C1 and KIR2DL3/2DL3-C1- were associated with decreased susceptibility for oculartoxoplasmosis and its clinical forms, while the KIR3DS1-/KIR3DL1+/Bw4-80Ile+ combination was associated as a protective factor against the development of oculartoxoplasmosis and, in particular, against recurrent manifestations. Our data demonstrate that activating and inhibitory KIRgenes may influence the development of oculartoxoplasmosis.