Research on intranasal delivery of drugs, peptides, and proteins has grown over the past decade as an alternate way to deliver substrates to the brain. Recent work has shown intranasal delivery of insulin in humans improves memory and cognition in healthy subjects as well as patients with Alzheimer’s disease. However, the molecular mechanism for the beneficial effect of insulin on memory has yet to be elucidated. To determine how intranasal insulin may be improving cognition, we utilized the SAMP8 mouse model of Alzheimer’s disease. These mice are known to develop cognitive impairments by 9 months of age and intranasal insulin can improve memory in 12-month old mice. We performed RNA sequencing analysis on the hippocampus in young SAMP8 mice and aged SAMP8 mice treated with and without insulin. While many genes and pathways were changed in our comparisons, we found genes were predominantly upregulated in 3 key pathways with age and downregulated with insulin administration. These pathways include the T cell receptor signaling pathway, cytokine-cytokine receptor interaction, and cell adhesion molecule pathway. Based on these inflammatory pathways driven by gene changes, we further investigated the impact of intranasal insulin on brain inflammation. This work further shows the important role of insulin in improving memory.