Images from the scene show Unit 3 has sustained major damage. While the worst of the damage seems to have affected the B&M store, the building also houses a Pets at Home pet store.
The unit also contains a pet store where a small number of animals are kept overnight. There have been no reported injuries and locals are being asked to avoid the area.
A spokeswoman for the Scottish Fire and Rescue Service said: More than 50 firefighters are currently tackling a fire within a large commercial unit in St Catherines Retail Park, Perth.
We were alerted at 2.13am on Saturday after reports of an alarm activation and mobilised a number of resources to the scene.
On arrival firefighters encountered a large, well-developed fire and 10 appliances and three aerial appliances are now on scene.
While crews continue to tackle this local residents are asked to avoid the area to allow access for emergency vehicles and due to road closures.
Early-morning rail services were disrupted but ScotRail has since confirmed that emergency services have allowed lines to be reopened.
More than 50 firefighters were called to St Catherines Retail Park shortly before 2.30am on Saturday.
A statement from the store said: “Im sorry to share with you there has been a fire last night at B&M in the St Catherines Retail Park in Perth which has partly spread to Pets at Home.
“I can confirm the animals in Pets at Home are fine due to having their own individual housing and fans. It seems that there has been minimal effects.”
Inspector Jennifer Reid said: “Our enquiries into this incident are at an early stage and we are working closely with the Scottish Fire and Rescue Service to establish the full circumstances.
“Around 30 animals have now been evacuated from Pets at Home and the majority of the retail park has now reopened.
A Scottish Fire and Rescue Service spokesman said: “We have mobilised more than ten fire engines to the scene and residents are asked to avoid the area due to road closures and to allow emergency service access.”