Background: The excessive exposure to silver nanoparticles (Ag-NPs) has raised concerns about their possible risks to the human health. The brain is a highly vulnerable organ to nano-silver harmfulness. The aim of this work was to evaluate the impacts of Ag-NPs exposure on the cerebellar cortex of rats. Methods: Rats were assigned to: Control, vehicle control and Ag-NP-exposed groups (at doses of 10 mg and 30 mg/kg/day). Samples were processed for light and electron microscopy examinations. Immunohistochemical localization of c-Jun N-terminal kinase (JNK), nuclear factor kappa beta (NF-κB) and calbindin D28k (CB) proteins was performed. Analyses of expression of DNA damage inducible transcript 4 (Ddit4), flavin containing monooxygenase 2 (FMO2) and thioredoxin-interacting protein (Txnip) genes were done. Serum levels of inflammatory cytokines were also measured. Results: Ag-NPs enhanced apoptosis as evident by upregulation of Ddit4 gene expressions and JNK protein immune expressions. Alterations of redox homeostasis were verified by enhancement of Txnip and FMO2 gene expressions, favoring the activation of inflammatory responses by increasing NF-κB protein immune expressions and serum inflammatory mediator levels. Another cytotoxic effect was the reduction of immune expressions of the calcium regulator CB. Conclusion: Ag-NPs exposure provoked biochemical, cellular and molecular changes of rat cerebellar cortex in a dose-dependent manner.