Extracellular vesicles (EVs) and their miRNA cargo are important regulators of intercellular communication, but their role in connecting respiratory inflammation in asthma with systemic metabolic alterations remains unclear. We hypothesized that HDM-induced allergic inflammation alters selected serum EV-derived miRNAs and that these changes are associated with molecular alterations in lung and adipose tissue. Serum EV-miRNAs from control and HDM-induced allergic rats were isolated by size-exclusion chromatography and analyzed using TaqMan Advanced miRNA Assays. Candidate rno-let-7b-5p targets were integrated with lung and adipose tissue microarray data, validated by qPCR, and assessed in silico using IntaRNA and DMISO. Among the 13 analyzed miRNAs, rno-let-7b-5p showed a nominally significant 1.5-fold increase in serum EVs from allergic rats (unadjusted p = 0.03); no multiple-testing correction was applied. Ptafr and Vav3 were enriched in lung inflammatory pathways, whereas Zbtb16 was downregulated in adipose tissue. qPCR confirmed increased pulmonary Ptafr expression (p = 0.00802) and reduced adipose Zbtb16 expression (p = 0.00034). Computational analyses yielded high-confidence predictions of interactions between rno-let-7b-5p and both genes, which require experimental validation. These preliminary, hypothesis-generating findings suggest that serum EV-associated rno-let-7b-5p may be associated with molecular alterations in the lung and adipose tissue during HDM-induced allergic inflammation. Confirmation in larger independent cohorts is required.