Objective To investigate whether dexmedetomidine (Dex) can modulate the effect of protein kinase A (PKA) on the improvement of propofol‑induced learning memory function and the effect on hippocampal pyroptosis in developing rats. Methods According to the random number table method, 120 7‑day‑old SD rats were divided into six groups (n=20): a control (Con) group, a propofol (Pro) group, a Dex group, a Dex pre‑administration (DP) group, a PKA specific antagonist (H89) + DP (HDP) group, and a dimethyl sulfoxide (DMSO) + DP (CDP) group. Rats in the Pro group were intraperitoneally injected with 50 mg/kg of propofol, followed by additional administration of 50 mg/kg propofol after the recovery of righting reflex (40‒60 min). The Con group was intraperitoneally injected with an equal amount of normal saline. The Dex group was intraperitoneally injected with 25 μg/kg of Dex. The DP group was intraperitoneally injected with 25 μg/kg of Dex, followed by the same administration regimen with the Pro group 20 min later. Both the HDP group and the CDP group were intraperitoneally injected with 0.05 mg/kg of H89 and DMSO at 0.1 ml, respectively, followed by the same administration regimen with the DP group 1 h later. The rats were raised in the same litter until 30 d of age. Then, the Morris water maze was used to detect the prolonged escape latency and the number of platform crossings. The levels of hippocampal phosphorylated‑PKA (p‑PKA), nucleotide‑binding domain leucine‑rich repeat and pyrin domain containing receptor 3 (NLRP3), caspase‑1, and gasdermin‑D protein (GSDMD) protein were detected by Western blot, while the lactate dehydrogenase (LDH) kit was utilized to detect hippocampal LDH concentrations. Results Compared with the Con group, the Pro, DP, HDP, and CDP groups showed prolonged escape latency, with a decreased number of platform crossings on days 2‒4 (all P<0.05); the levels of hippocampal p‑PKA protein decreased, while the levels of NLRP3, caspase‑1, and GSDMD protein and LDH concentrations increased (all P<0.05). Compared with the Pro group, the Dex, DP, and CDP groups presented shortened escape latency, with an increasing number of platform crossing on days 2‒4 (all P<0.05); the levels of hippocampal p‑PKA protein increased, while the levels of NLRP3, caspase‑1, and GSDMD protein and LDH concentrations decreased (all P<0.05). Compared with the DP and CDP groups, the HDP group showed prolonged escape latency, with a reduced number of platform crossings on days 2‒4 (all P<0.05); the levels of hippocampal p‑PKA protein decreased, while the levels of NLRP3, caspase‑1, and GSDMD protein and LDH concentrations increased (all P<0.05). There was no significant difference in other indexes (all P>0.05). Conclusions Dex can improve propofol‑induced learning memory impairment in developing rats, which may be related to the activation of PKA to down‑regulate the NLRP3/caspase‑1 signaling pathway, in order to relieving hippocampal pyroptosis.