SummaryInvasive aspergillosis has become an increasing problem in immunocompromised patients in recent years. Due to increased antimicrobial resistance, natural agents with medicinal and immunomodulatory effects have gained more attention. Honey is a natural substance with documented antimicrobial, anti-inflammatory and wound healing effects. In this study the effects of three Iranian honeys on some aspects of innate immunity and survival rate during invasive aspergillosis were investigated. For this purpose, mice were divided into 10 groups (honey alone, honey and infection, negative and positive controls) each containing 10 individuals. Mice were treated with honey (1.5g/kg BW/orally) for 10 days. At day 6, Aspergillus fumigatus conidia (5 × 105/ml) were injected intravenously to the infected groups. Mice were euthanized at day 11, and spleen and peritoneal cell culture was performed. Pro-inflammatory cytokine production using ELISA and killing assay was also performed. For survival rate, 10 mice from each infected group were considered and monitored for 30 days. The results showed that honey treatment could significantly increase IL6 and IL1β production in infected mice as well as improve macrophage killing (p < 0.05). Also mice treated with honey had a greater survival time than the infected group. Our results suggest that honey could boost the immune system and increase survival time in invasive aspergillosis.