Dufner has not played competitively since he was forced to abandon the defence of his US PGA Championship title in August after struggling through 10 holes at Valhalla.
Neck and shoulder problems ensured the 37-year-old American missed the subsequent Ryder Cup at Gleneagles, but he is hopeful he can remain pain-free this week in an event co-sanctioned by the European Tour and the PGA Tour of Australasia.
Dufner is quoted by the European Tour website as saying: "I've had a couple of issues with my neck and shoulder and tightness trapping nerves, which gave me a dead arm. But it's feeling a lot better and I'm heading in the right direction.
"I was pretty much out of commission for about six to eight weeks. I didn't do much of anything for six weeks, just a lot of treatment. Then it was strengthening work for my shoulder, and then I slowly started to work on some other areas to get stronger, and then back into golf.
"This week will be five days in a row playing, which I haven't done, so we will see how it goes."
Dufner - the runner-up to Bo Van Pelt in Perth two years ago - is one of three major champions in the field at Lake Karrinyup Country Club, with Charl Schwartzel - victor at the Masters in 2011 - and 2006 US Open winner Geoff Ogilvy also present.
South Korea's Jin Jeong is the defending champion and will be seeking a return to form after making just six cuts in 22 appearances this season.
"I haven't been playing great for the last four or five months, but I've been hitting it pretty well this week so far so I think being here is helping me," said Jeong, who resides in Melbourne.
"I always enjoy this place. The course really suits my game."
The Perth International is the final event of the European Tour's regular season, so there is much pressure on the players yet to retain their card.
England's Matthew Nixon currently occupies 111th position on the Race to Dubai, the final spot that guarantees retention of playing privileges, while Irishman Kevin Phelan will be seeking to follow up a third-placed finish at the Hong Kong Open last week, which saw him climb from 152nd to 130th.
Low scoring can perhaps be anticipated, given that Lake Karrinyup was the venue when Ernie Els set a new European Tour record for the lowest 72-hole total in relation to par [a 29-under 259] at the 2003 Johnnie Walker Classic.