Postmortem molecular analysis of the human brain during development and aging suggests there are epigenetic changes reflecting early life experiences. This includes changes in the expression of non-coding RNAs such as miRNA. These molecules alter the regulation of gene expression and can interact with underlying genetic risk factors, contributing to neurological and neuropsychiatric syndromes such as schizophrenia. The aim of the current study was to investigate the role of miRNA in the brains’ response to maternal immune activation and adolescent cannabis exposure, alone and in combination, as both have been identified as environmental risk factors for this disorder. Pregnant Wistar rats were administered the viral mimic polyriboinosinic-polyribocytidilic acid (poly-I:C) or vehicle on embryonic day 15. Male offspring were treated daily with synthetic cannabinoid HU210, or vehicle, from post-natal day (PND) 35 for 14 days and euthanized on PND 55. Whole genome miRNA microarrays were performed on the left and right entorhinal cortex (EC) and whole genome mRNA microarrays on the left EC, as abnormalities in this region have been associated with schizophrenia. We found exposure to both poly-I:C and HU210 significantly altered miRNA expression in the left hemisphere as compared to the right. These changes were dominated by a large subgroup of miRNA transcribed from a single imprinted locus on chromosome 6q32. The syntenic human locus (14q32) encodes a large proportion of miRNAs found to be differentially expressed in patients with schizophrenia. Genes identified as potentially regulated by differentially expressed miRNA encode proteins with prominent functions in neuronal growth and differentiation; development of specific cortical layers; synaptic plasticity and transmission; axonogenesis; GABA neurotransmitter system; and learning and memory formation. These findings indicate that the interaction of both an early and late environmental insult can enhance changes in offspring miRNA expression in the EC with possible outcomes relevant to schizophrenia in adulthood.