BackgroundThe female reproductive tract is exposed directly to the male’s ejaculate, making it a hotspot for mating-induced responses. InDrosophila melanogaster, changes in the reproductive tract are essential to optimize fertility. Many changes occur within minutes after mating, but such early timepoints are absent from published RNA-seq studies. We measured transcript abundances using RNA-seq and microRNA-seq of reproductive tracts of unmated and mated females collected at 10–15 min post-mating. We further investigated whether early transcriptome changes in the female reproductive tract are influenced by inhibiting BMPs in secondary cells, a condition that depletes exosomes from the male’s ejaculate.ResultsWe identified 327 differentially expressed genes. These were mostly upregulated post-mating and have roles in tissue morphogenesis, wound healing, and metabolism. Differentially abundant microRNAs were mostly downregulated post-mating. We identified 130 predicted targets of these microRNAs among the differentially expressed genes. We saw no detectable effect of BMP inhibition in secondary cells on transcript levels in the female reproductive tract.ConclusionsOur results indicate that mating induces early changes in the female reproductive tract primarily through upregulation of target genes, rather than repression. The upregulation of certain target genes might be mediated by the mating-induced downregulation of microRNAs. Male-derived exosomes and other BMP-dependent products were not uniquely essential for this process. Differentially expressed genes and microRNAs provide candidates that can be further examined for their participation in the earliest alterations of the reproductive tract microenvironment.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12864-023-09397-z.