In human ocular toxoplasmosis, serotype is related with greater severity. We analyzed Toxoplasma GRA6 serotype in 23 patients with ocular toxoplasmosis (13 confirmed, two co-infections- and eight unconfirmed cases) and 20 individuals chronically infected with Toxoplasma but without ocular involvement. In patients with ocular toxoplasmosis, we also studied host gene polymorphisms related to immune response (IL-1β; IL-1α; IL-10; IFN-γ; TNF-α, IL-12), IL-17R, TLR-9, and P2RX7. Additionally, eight patients were studied for the production of TNFα, IL1-β, IFN−γ and IL-10 by their peripheral leukocytes after ex vivo stimulation with soluble Toxoplasma antigens. There were no differences in the distribution of serotypes (GRA6-I versus GRA6 non-I) between infected individuals with- or without ocular involvement. Seropositivity for GRA6-I was associated with higher number of retinal lesions and higher levels of IL-1β. Two polymorphisms were associated with specific clinical manifestations of ocular toxoplasmosis: IL-10 -819 C/T with bilateral lesions and IL-12 + 169,774 A/C with synechia. Higher levels of IL-10 were found in patients with the allele G/G at the polymorphic region IL-10 -1082. People with a GRA6 I serotype and possessing the allele G/G at the polymorphic region TNFα-857 suffered from an increased number of retinal lesions. We found a positive association between host cytokine genes polymorphisms and GRA6 serotypes correlated with specific clinical manifestations and immune response in ocular toxoplasmosis.